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Xiao-Tian Zhang,* Zhen-Yang Mao,* Xiang-Yun Jin, Yu-Gang Wang, Yu-Qi Dong, Chao Zhang Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Zhang; Yu-Qi Dong, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong New Area, Shanghai, People’s Republic of China, Tel +86-13817307997 ; +86-13331873590, Email drzhangchao@sina.coml; dyqrjgk@126.comPurpose: Delayed skin healing in diabetic wounds is a major clinical problem. The tRNA-derived small RNAs (tsRNAs) were reported to be associated with diabetes. However, the role of tsRNAs in diabetic wound healing is unclear. Our study was designed to explore the tsRNA expression profile and mine key potential tsRNAs and their mechanism in diabetic wounds.Methods: Skin tissues of patients with diabetic foot ulcers and healthy controls were subjected to small RNA sequencing. The role of candidate tsRNA was explored by loss- and gain-of-function experiments in HUVECs.Results: A total of 55 differentially expressed tsRNAs were identified, including 12 upregulated and 43 downregulated in the diabetes group compared with the control group. These tsRNAs were mainly concentrated in intercellular interactions and neural function regulation in GO terms and enriched in MAPK, insulin, FoxO, calcium, Ras, ErbB, Wnt, T cell receptor, and cGMP-PKG signaling pathways. tRF-Gly-CCC-039 expression was upregulated in vivo and in vitro in the diabetic model. High glucose disturbed endothelial function in HUVECs, and tRF-Gly-CCC-039 mimics further harmed HUVECs function, characterized by the suppression of proliferation, migration, tube formation, and the expression of Coll1a1, Coll4a2, and MMP9. Conversely, the tRF-Gly-CCC-039 inhibitor could attenuate high-glucose-induced endothelial injury to HUVECs.Conclusion: We investigated the tsRNAs expression profile in diabetic foot ulcers and defined the impairment role of tRF-Gly-CCC-039 in endothelial function in HUVECs. This study may provide novel insights into accelerating diabetic skin wound healing.Keywords: diabetic foot ulcers, skin healing, tsRNA expression profile, tRF-28-Q1Q89P9L84DF, endothelial damage

Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel

Yu-Fei Qian,1 Gui-Ling Geng,1 Yu-Qin Ren,2 Xin-Tong Zhang,2 Wen-Jun Sun,2 Qing Li2 1Department of School of Nursing, Nantong University Medical School, Nantong, 226001, People’s Republic of China; 2Department of Emergency, Nantong First People’s Hospital, Nantong, 226006, People’s Republic of ChinaCorrespondence: Gui-Ling GengDepartment of School of Nursing, Nantong university Medical school, No. 19, Qixiu Road, Nantong City, Jiangsu Province, 226001, People’s Republic of ChinaTel +86 15152889466Fax +86-513-85051876Email geng_gl@126.comObjective: This study aimed to investigate community residents’ awareness of basic life support (BLS) and their willingness to attempt rescue.Methods: From October to December 2020, in the communities of Nantong City, a stratified three-stage random sampling method was adopted to select residents from 12 neighborhood committees over the age of 18 with whom to conduct a cross-sectional questionnaire survey. A self-designed questionnaire was adopted, the contents of which included the general situation of the respondent, knowledge, attitude, and behavior in relation to BLS; the Cronbach’s α coefficient of the questionnaire was 0.719.Results: A total of 3000 questionnaires were distributed, of which 2812 were valid, with a valid response rate of 93.73%. Of the 2812 respondents, 41.18% had seen an automatic external defibrillator (AED), 48.83% had experience of’ cardiopulmonary resuscitation (CPR), and 25.07% of the respondents had experience of’ AEDs. When an accident occurred, 50.50% of residents were willing to attempt rescue, 70.80% were willing to attempt rescue under professional guidance, and 71.23% were willing to attempt rescue after learning BLS techniques. Of the residents who were unwilling to attempt rescue, 32.75% were worried about their lack of ability, 27.91% were concerned about legal issues, 14.01% feared infectious diseases, and 10.35% were unwilling to perform mouth-to-mouth artificial respiration. Age, occupation, education level, and whether they had participated in first aid training were the influencing factors.Conclusion: Residents in Nantong have less knowledge of BLS, and their knowledge of CPR is better than that of AEDs. Residents have a strong willingness to learn BLS. Measures need to be taken to improve their understanding of BLS and their application skills. Residents have high levels of willingness to attempt rescue, but a certain percentage of residents have concerns. Interventions can be made to target the different reasons.Keywords: out-of-hospital cardiac arrest, basic life support, automatic external defibrillator, rescue willing

Xin Tong Zhang,* Song Song Shi,* Yu Qin Ren, Li Wang Department of Emergency, Nantong First People’s Hospital, Nantong, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Qin RenDepartment of Emergency, Nantong First People’s Hospital, No. 6 of Haierxiang North Road, Chongchuan District, Nantong, 226001, People’s Republic of ChinaTel +86 15962956088Email renyuqindr@21cn.comObjective: Post-traumatic growth (PTG) is a positive result of fighting against traumatic events. This study aimed to investigate the current status of PTG of clinical nurses and analyze its influencing factors.Methods: A total of 1790 nurses participated in the study and completed the questionnaire. Demographic data and related scales of PTG, post-traumatic stress disorder, coping style, social support, and self-efficacy were collected online. Through univariate analysis and multiple linear regression analysis, the related influencing factors were studied.Results: The total score of PTG of 1790 nurses was 67.17 ± 14.79. The analysis revealed that good social support and self-efficacy were important factors to improve the level of PTG of clinical nurses, while bad psychological state and working for many years were the negative factors of PTG.Conclusion: Good social support and self-efficacy can help clinical nurses cope with the novel coronavirus disease 2019 pandemic and accept the disease’s challenges. If these factors can be considered in clinical practice, this will help promote clinical nurses’ mental health.Keywords: COVID-19, post-traumatic growth, psychological impact, nurse, influencing factors

Background: The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure., Methods and Results: The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis-4 score (FIB-4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB-4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB-4: odds ratio [OR], 1.15 [95% CI, 1.07-1.23]; NFS: OR, 1.42 [95% CI, 1.23-1.64]; APRI: OR, 1.44 [95% CI, 1.15-1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB-4 ≥2.67 versus FIB-4 <1.3: OR, 2.18 [95% CI, 1.47-3.24]; NFS ≥0.675 versus NFS <-1.455: OR, 2.53 [95% CI, 1.37-4.68]). Subgroup analysis found that the association between APRI and heart failure was stronger in female patients., Conclusions: In the general US population, the prevalence of advanced liver fibrosis risk varied between 0.35% and 8.06% as indicated by noninvasive liver fibrosis scores. FIB-4, NFS, and APRI scores were linked to an elevated prevalence of heart failure.

Background: Cancer cachexia significantly contributes to morbidity and mortality in patients with non-small-cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin-6 (IL-6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL-6-elevated cachexia., Methods: In this retrospective study, data were collected from patients with NSCLC and concurrent IL-6-elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C-reactive protein (CRP) and mGPS. Qualitative improvements in patient self-rated appetite and fatigue were reported as exploratory analysis., Results: The study included 49 patients diagnosed with NSCLC and IL-6-elevated cachexia, Eastern Cooperative Oncology Group performance status of 2-4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08-0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75-1.00; p < 0.001). Over the 12-week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. -5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. -2.97 ± 0.71 g/L, p < 0.001; CRP: -91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: -1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab-related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection., Conclusion: Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL-6-elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy., (© 2024. The Author(s).)

Purpose: To explore the utility of high frequency oscillations (HFO) and long-range temporal correlations (LRTCs) in preoperative assessment of epilepsy., Methods: MEG ripples were detected in 59 drug-resistant epilepsy patients, comprising 5 with parietal lobe epilepsy (PLE), 21 with frontal lobe epilepsy (FLE), 14 with lateral temporal lobe epilepsy (LTLE), and 19 with mesial temporal lobe epilepsy (MTLE) to identify the epileptogenic zone (EZ). The results were compared with clinical MEG reports and resection area. Subsequently, LRTCs were quantified at the source-level by detrended fluctuation analysis (DFA) and life/waiting -time at 5 bands for 90 cerebral cortex regions. The brain regions with larger DFA exponents and standardized life-waiting biomarkers were compared with the resection results., Results: Compared to MEG sensor-level data, ripple sources were more frequently localized within the resection area. Moreover, source-level analysis revealed a higher proportion of DFA exponents and life-waiting biomarkers with relatively higher rankings, primarily distributed within the resection area (p<0.01). Moreover, these two LRCT indices across five distinct frequency bands correlated with EZ., Conclusion: HFO and source-level LRTCs are correlated with EZ. Integrating HFO and LRTCs may be an effective approach for presurgical evaluation of epilepsy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of bacterial resistance significantly contributes to the persistence of infections. Although previous studies have highlighted the benefits of metal-doped positive carbon nanodots in managing bacterial wound infections, their mechanism of action is relatively simple and they may pose potential hazards to human cells. Therefore, it is essential to develop a one-stop carbon dot nanoplatform that offers high biocompatibility, antibacterial properties, and anti-inflammatory activities for wound infection management. This study explores the antibacterial efficacy, without detectable resistance, and wound-healing potential of nitrogen-doped (N-doped) negatively charged carbon dots (TPP-CDs). These carbon dots are synthesized using tannic acid (TA), polyethylene polyamine, and polyethylene glycol (PEG) as precursors, with a focus on their biocompatibility. Numerous systematic studies have shown that TPP-CDs can effectively destroy bacterial biofilms and deoxyribonucleic acid (DNA), while also inducing oxidative stress, leading to a potent antimicrobial effect. TPP-CDs also demonstrate the ability to scavenge excess free radicals, promote cellular proliferation, and inhibit inflammatory factors, all of which contribute to improved wound healing. TPP-CDs also demonstrate favorable cell imaging capabilities. These findings suggest that N-doped negatively charged TPP-CDs hold significant potential for treating bacterial infections and offer practical insights for their application in the medical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Acute liver injury (ALI) is an abnormal liver function caused by oxidative stress, inflammation and other mechanisms.The interaction between intestine and liver plays an important role in ALI, and natural polysaccharides can participate in the regulation of ALI by regulating the composition of intestinal flora. In this study, Ganoderma lucidum polysaccharide was used as the research object, and ICR mice were used to construct an acute liver injury model induced by carbon tetrachloride (CCl 4 ). 16S rRNA sequencing technology was used to analyze the flora structure abundance and detect the changes of intestinal flora. The effective reading of 8 samples was obtained by 16S rRNA sequencing technology, and a total of 1233 samples were obtained. The results of alpha diversity analysis showed that the sequencing depth was sufficient, the abundance of species in the samples was high and the distribution was uniform, and the sequencing data of the samples was reasonable. Nine species with significant differences were screened out by abundence analysis of intestinal flora structure at genus level. Beta diversity analysis showed that species composition was different between the model group and the treatment group. Ganoderma lucidum polysaccharide can maintain the integrity of mucosal barrier by promoting the proliferation of intestinal epithelial cells and anti-oxidative stress injury, thereby improving the intestinal mucosal inflammation of mice, regulating intestinal flora, and effectively alleviating CCl 4 -induced acute liver injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a 'main active ingredient-target' network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The tumor necrosis factor (TNF) protein was verified by Western blot; Twenty one active ingredients in GL and 142 corresponding targets were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer's disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI. GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer's disease pathway and TNF protein., (© 2024 The Author(s).)

Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC., Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment., Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49)., Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-274/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Aim: To observe the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) secretions on the relevant factors in mouse retinal astrocytes, and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A (VEGF-A) and to observe the therapeutic effect on the mouse model of retinopathy of prematurity (ROP)., Methods: Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia group. MTT assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect related indicators. Possible mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were explored. At last, the efficacy of exosomes of UCMSCs in a mouse ROP model was explored. Graphpad6 was used to comprehensively process data information., Results: The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient ultracentrifugation. Reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased, and the ROP cell model was established after 6h of hypoxia. The secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α, the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration dependent. Compared with the ROP cell model group, the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway related factors in the hUCMSCs exocrine group is significantly decreased. The intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1α in ROP model tissues. HE staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs secretion., Conclusion: In a hypoxia induced mouse retinal astrocyte model, hUCMSCs exosomes are found to effectively reduce the expression of HIF-1α and VEGF-A, which are positively correlated with the concentration of hUCMSCs exosomes. HUCMSCs exosomes can effectively reduce the number of retinal neovascularization and the expression of HIF-1α and VEGF-A proteins in ROP mice, and are positively correlated with drug dosage. Besides, they can reduce the related factors on the PI3K/AKT/mTOR signaling pathway., Competing Interests: Conflicts of Interest: Zhang XT, None; Zhao BW, None; Zhang YL, None; Chen S, None., (International Journal of Ophthalmology Press.)

Rationale and Objectives: Traditional Ki-67 evaluation in breast cancer (BC) via core needle biopsy is limited by repeatability and heterogeneity. The automated breast ultrasound system (ABUS) offers reproducibility but is constrained to morphological and echoic assessments. Radiomics and machine learning (ML) offer solutions, but their integration for improving Ki-67 predictive accuracy in BC remains unexplored. This study aims to enhance ABUS by integrating ML-assisted radiomics for Ki-67 prediction in BC, with a focus on both intratumoral and peritumoral regions., Materials and Methods: A retrospective analysis was conducted on 936 BC patients, split into training (n = 655) and testing (n = 281) cohorts. Radiomics features were extracted from intra- and peritumoral regions via ABUS. Feature selection involved Z-score normalization, intraclass correlation, Wilcoxon rank sum tests, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator logistic regression. ML classifiers were trained and optimized for enhanced predictive accuracy. The interpretability of the optimized model was further augmented by employing Shapley additive explanations (SHAP)., Results: Of the 2632 radiomics features in each patient, 15 were significantly associated with Ki-67 levels. The support vector machine (SVM) was identified as the optimal classifier, with area under the receiver operating characteristic curve values of 0.868 (training) and 0.822 (testing). SHAP analysis indicated that five peritumoral and two intratumoral features, along with age and lymph node status, were key determinants in the predictive model., Conclusion: Integrating ML with ABUS-based radiomics effectively enhances Ki-67 prediction in BC, demonstrating the SVM model's strong performance with both radiomics and clinical factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population., Study Design: Retrospective., Setting: Clinical data in the National COVID Cohort Collaborative database (N3C)., Methods: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period., Results: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; P < 0.001), alpha (OR, 3.63; CI, 3.48-3.78; P < 0.001), delta (OR, 3.03; CI, 2.94-3.12; P < 0.001), omicron 21K variant (OR, 2.97; CI, 2.90-3.04; P < 0.001), and omicron 23A variant (OR, 8.80; CI, 8.35-9.27; P < 0.001)., Conclusions: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings., Competing Interests: None declared., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application., Aim: To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs., Methods: The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification., Results: In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation., Conclusion: Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis ) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro . Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Objective: To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy., Methods: A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F)., Results: In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728-1.000) and 0.809 (0.561-1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510-1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p < 0.05)., Conclusion: The Nomo-LDLM-2F score derived from multi-lesion and time series CT images holds promise for the effective readout of OS probability in patients with HER2-positive stage IV GC receiving anti-HER2 therapy., Critical Relevance Statement: The deep learning model using baseline and early follow-up CT images aims to predict OS in patients with stage IV gastric cancer receiving anti-HER2 targeted therapy. This model highlights the spatiotemporal heterogeneity of stage IV GC, assisting clinicians in the early evaluation of the efficacy of anti-HER2 therapy., Key Points: • Multi-lesion and time series model revealed the spatiotemporal heterogeneity in anti-HER2 therapy. • The Nomo-LDLM-2F score was a valuable prognostic marker for anti-HER2 therapy. • CT-based deep learning model incorporating time-series tumor markers improved performance., (© 2024. The Author(s).)

Introduction: Objective: the Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status of patients. We aimed to investigate the value of CONUT score on predicting length of hospital stay (LOS) and the risk of long COVID in patients with COVID-19. Methods: a total of 151 patients with COVID-19 were enrolled for analysis. Patients were followed up for two years from three months after the onset of SARS-CoV-2 infection. CONUT score was calculated on admission. The correlation between CONUT score and LOS were assessed by Spearman's rank correlation coefficient and multivariate linear analysis. The association between different CONUT grade and long COVID was evaluated by Kaplan-Meier survival curves with log-rank test and Cox proportional hazard models. Results: Spearman's rank correlation coefficient showed that CONUT scores were positively correlated with LOS (r = 0.469, p < 0.001). Multivariate linear analysis showed that CONUT score is the only independent determinant of LOS (B 2.055, 95 % CI: 1.067-3.043, p < 0.001). A total of 53 (35.10 %) patients with long COVID were identified. Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses showed that the incidence of long COVID in patients with a higher CONUT score was significantly higher than in patients with lower CONUT score (p < 0.001). Conclusions: higher CONUT score predicts longer LOS and the risk of long COVID in patients with COVID-19. The CONUT score might be useful for risk stratification in COVID-19 patients and help to develop new nutritional treatment strategies for long COVID.

Introduction: Pyruvate kinase M2 (PKM2) was involved in the pathophysiology of atherosclerosis and coronary artery disease (CAD). We tested whether plasma PKM2 concentrations were correlated with clinical severity and major adverse cardiovascular events (MACEs) in CAD patients., Materials and Methods: A total of 2443 CAD patients and 238 controls were enrolled. The follow-up time was two years. Plasma PKM2 concentrations were detected by enzyme-linked immunosorbent assay (ELISA) kits (Cloud-Clone, Wuhan, China) using SpectraMax i3x Multi-Mode Microplate Reader (Molecular Devices, San Jose, USA). The predictors of acute coronary syndrome (ACS) were assessed by logistic regression analysis. The association between PKM2 concentration in different quartiles and MACEs was evaluated by Kaplan-Meier (KM) curves with log-rank test and Cox proportional hazard models. The predictive value of PKM2 and a cluster of conventional risk factors was determined by Receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) were utilized to evaluate the enhancement in risk prediction when PKM2 was added to a predictive model containing a cluster of conventional risk factors., Results: In CAD patients, PKM2 concentration was the independent predictor of ACS (P < 0.001). Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses revealed that patients with a higher PKM2 concentration had higher incidence of MACEs compared to those with a lower PKM2 concentration (P < 0.001). The addition of PKM2 to a cluster of conventional risk factors significantly increased its prognostic value of MACEs., Conclusion: Baseline plasma PKM2 concentrations predict the clinical severity and prognosis of CAD., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Objective: To investigate the efficacy and safety of bupivacaine liposome for pericapsular nerve group block (PENGB) for postoperative analgesia in elderly patients with total hip replacement. Methods: A total of 42 elderly patients underwent total hip replacement were selected in the Second Affiliated Hospital of Wenzhou Medical University from May to July in 2023, including 19 males and 23 females, aged (68.8±6.3) years, the American Society of Anesthesiologists (ASA) grade Ⅰ to Ⅲ. They were divided into bupivacaine liposome group (observation group) and levobupivacaine hydrochloride group (control group) according to random number table, with 21 cases in each group. All the patients were anesthetized by lumbar anesthesia combined with PENGB. During PENGB, the observation group was injected with 10 ml (133 mg) bupivacaine liposome+5 ml normal saline, and the control group was injected with 10 ml (75 mg) levobupivacaine hydrochloride+5 ml normal saline. The primary outcome measures included the rest and movement visual analogue scale (VAS) scores at 6, 12, 24, 36, 48, 60, and 72 h after operation, the sufentanil consumption in analgesic pump, the numbers of analgesic pump compressions, and the rates of additional parexib sodium use in ward. The secondary outcome measures were the changes in lower limb muscle strength, the length of hospital stay and the occurrence of adverse reactions. Results: There was no significant difference in the rest and movement VAS scores between the two groups at pre-operation and at 6 h after operation ( P >0.05);but the rest and movement VAS scores at 12, 24, 36, 48, 60 and 72 h after operation in observation group were significantly lower than those in control group ( P <0.05); the rest and movement VAS scores at 6, 12, 24, 36, 48, 60 and 72 h after operation were lower than those at pre-operation in two group ( P <0.05). The consumption of sufentanil in analgesic pump and parexib sodium usage in observation group were lower than those in control group at 12, 24, 36 and 48 h after operation ( P <0.05). The total number of analgesic pump compressions, the number of effective compressions and the number of ineffective compressions in 48 h in observation group were lower than those in control group ( P <0.05). The muscle strength of the lower limbs of all patients were able to move against gravity at 12 h after operation. The incidence of nausea in 48 h after operation in observation group was 9.5% (2/21), which was lower than 42.9% (9/21) in control group ( P =0.014). No postoperative vomiting occurred in all patients. The length of the hospital stay was (9.3±2.2) d in observation group and (8.9±1.9) d in control group, and there was no significant difference between the two groups ( P =0.500). Conclusion: Compared with levobupivacaine hydrochloride, liposomal bupivacaine in PENGB provides analgesic effects for up to 72 h after total hip replacement in elderly patients, reduces postoperative opioid and other analgesics usage, decreases the incidence of postoperative nausea, and has a minor effect on lower limb movement without prolonging hospitalization.

Background: Wheat is one of the main grain crops in the world, and the tiller number is a key factor affecting the yield of wheat. Phosphorus is an essential element for tiller development in wheat. However, due to decreasing phosphorus content in soil, there has been increasing use of phosphorus fertilizer, while imposing risk of soil and water pollution. Hence, it is important to identify low phosphorus tolerance genes and utilize them for stress resistance breeding in wheat., Results: We subjected the wheat variety Kenong 199 (KN199) to low phosphorus stress and observed a reduced tiller number. Using transcriptome analysis, we identified 1651 upregulated genes and 827 downregulated of genes after low phosphorus stress. The differentially expressed genes were found to be enriched in the enzyme activity regulation related to phosphorus, hormone signal transduction, and ion transmembrane transport. Furthermore, the transcription factor analysis revealed that TaWRKY74s were important for low phosphorus tolerance. TaWRKY74s have three alleles: TaWRKY74-A, TaWRKY74-B, and TaWRKY74-D, and they all belong to the WRKY family with conserved WRKYGQK motifs. These proteins were found to be located in the nucleus, and they were expressed in axillary meristem, shoot apical meristem(SAM), young leaves, leaf primordium, and spikelet primordium. The evolutionary tree showed that TaWRKY74s were closely related to OsWRKY74s in rice. Moreover, TaWRKY74s-RNAi transgenic plants displayed significantly fewer tillers compared to wild-type plants under normal conditions. Additionally, the tiller numebr of the RNAi transgenic plants was also significantly lower than that of the wild-type plants under low-phosphorus stress, and increased the decrease amplitude. This suggestd that TaWRKY74s are related to phosphorus response and can affect the tiller number of wheat., Conclusions: The results of this research showed that TaWRKY74s were key genes in wheat response to low phosphorus stress, which might regulate wheat tiller number through abscisic acid (ABA) and auxin signal transduction pathways. This research lays the foundation for further investigating the mechanism of TaWRKY74s in the low phosphorus environments and is significant for wheat stress resistance breeding., (© 2023. The Author(s).)

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background: There are many available treatment options for keloid; however, single treatments are usually less effective. Therefore, more scientifically rational and effective combined treatment methods should be sought to solve the pain associated with keloids., Aim: To explore the efficacy and safety of surgical resection and ultra-reduced tension suture combined with superficial radiation as keloid treatment., Methods: Fifteen keloid patients admitted to Qingdao Eighth People's Hospital from June 2020 to January 2022 were enrolled in this retrospective analysis. All patients underwent a comprehensive treatment approach comprising surgical resection, ultra-reduced tension suture incision, and superficial radiation therapy within 24 h postoperatively. The modified Vancouver Scar Scale (mVSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to evaluate the treatment effect, whereas the efficacy, adverse effects, and recurrence rate were observed according to the 12-mo follow-up after treatment., Results: The mVSS and POSAS scores at 1 and 6 mo after combination treatment decreased compared to before treatment ( P < 0.001), and the overall response rate was 93.3%. Only one case recurred, yielding a 6.7% recurrence rate. The incidence of local chromour sedimentation rate in 1-3 mo after radiotherapy was 33.3% (5 patients), all subsiding after 6-9 mo, without complications, such as delayed wound healing or dermatitis., Conclusion: Surgical resection, super subtraction sutures, and superficial radiotherapy are treatment methods with short courses, low recurrence rates, and good safety profiles., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest related to this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function., Methods: In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference., Results: AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm 2 than that at 3 months postoperatively ((278.0 ± 26.2) mm 2 , t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm 2 , t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period., Conclusion: Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Objective: To evaluate adolescent pelvic coronal inclination angle change after flatfoot treated with arthroereisis. Method: A case-series study. From June 2018 to September 2020, 25 children with flexible flat foot and pelvic obliquity were included in this retrospective study in Peking University Shenzhen Hospital. There were 17 males and 8 females with a mean age of (11.2±2.2) years (9-15 years). There were 5 cases of unilateral flatfoot and 20 cases of bilateral flatfoot. All of the patients were surgically treated with arthroereisis. Regular follow-up was done in 3 months, 1 and 2 years postoperatively. Weightbearing fluoroscopy of entire lower limb and foot were investigated to measure Meary's angle, calcaneal pitch angle, height difference at ankle and pelvic plane, pelvic inclination and sacrum-iliac distance (F value) on coronal plane. Results: The mean Mearys' angle at 3 month postoperatively was improved when compared with that before the operation (3.1°±1.5° vs 25.9°±4.3°, P <0.001), and it remained at the same level 2 years after the operation (compared with that at 1 year after the operation, P =0.748). The calcaneal pitch angle improved significantly at 3-month follow-up when compared with that before the operation (16.6°±2.4° vs 9.9°±1.5°, P <0.001), and there was no significant change between 1 year and 2 years after operation ( P =0.542). The height difference at mortise plane were also reduced at the 3-month follow-up( P <0.001), and it remained at the same level at 1 year and 2 years after the operation ( P =0.159). Pelvic height difference decreased dramatically from (12.4±1.7) mm (before operation) to (7.1±1.2) mm(3 month after the operation) ( P <0.001), it decreased to (3.6±1.8) mm 1 year after the operation (compared with that at 3 months after the operation, P <0.001), and no further reduction was observed 2 years after the surgery ( P =0.483). The pelvic inclination angle and sacrum-iliac distance were also improved at 3-month follow-up when compared with those before the operation (both P <0.001), and they declined further 1 year after the operation(both P <0.05), but the decreasing trend disappeared at the 2-year follow-up (both P >0.05). Conclusion: For adolescent flexible flat foot patients with pelvic obliquity, the coronal inclination and pelvic height discrepancy would partially recovered with correction of flatfoot deformity, but it could not be completely corrected in the mean follow-up period of 2 years after the operation.

Aims: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants., Methods and Results: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography., Conclusion: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse reaction to chemotherapeutics, which seriously affects the outcome of chemotherapy and patients' quality of life. Although it is commonly seen, it lacks effective treatment. Our previous study found that ozone could alleviate neuropathic pain. Damage-associated molecular patterns (DAMPs) or Toll-like receptor 4 (TLR4) or tissue factor (TF)-mediated neuroinflammation and microcirculation disturbance is the main reason for CIPN. Suppressors of cytokine signaling (SOCS) 3 is an endogenous negative feedback regulator of inflammation via TLR4 inhibition., Materials and Methods: Oxaliplatin (L-OHP) was used to establish mice's CIPN model. Nociceptive responses were assessed by observing the ICR mice's incidence of foot regression in mechanical indentation response experiments. Cell signaling assays were performed by Western blotting and immunohistochemistry. The mouse leukemia cells of monocyte-macrophage line RAW 264.7 were cultured to investigate the effects of ozone administration on macrophage., Results: Ozone decreased the expression of TF in the blood and sciatic nerve. It upregulated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-SOCS3 axis to relieve CIPN and inhibit TF expression in vivo. SOCS3 expression was induced by ozone to inhibit the p38/TF signaling in RAW 246.7 cells. Ozone also prevented L-OHP-induced sciatic nerve demyelination. Microglia activation was inhibited, and c-Fos and calcitonin gene-related peptide (CGRP) expression was decreased in the spinal dorsal horn via ozone., Conclusions: In this study, we demonstrated that ozone could alleviate CIPN by upregulating the AMPK-SOCS3 axis to inhibit TF expression, which is a potential treatment for CIPN.

Research on the use of polysaccharides as hydrophobic bioactive carriers instead of proteins is still scarce. Sugar beet pectin (SBP) contains a small amount of protein and is a potential carrier for loading curcumin. In this work, SBP encapsulation, genipin crosslinking, and laccase-induced gelation were used to develop novel jelly food and improve the stability of curcumin without the incorporation of oil. By mixing the SBP solution (40 mg/mL) with curcumin powder (25 mg/mL SBP solution), an SBP-curcumin complex (SBP-Cur) was fabricated with a loading amount of 32 mg/g SBP, and the solubility of curcumin improved 116,000-fold. Fluorescence spectroscopy revealed that hydrophobic interactions drove the complexation of curcumin and SBP. Crosslinked by genipin (10 mM), SBP-Cur showed a dark blue color, and the gel strength of laccase-catalyzed gels was enhanced. Heating and UV radiation tests suggested that the genipin crosslinking and gelation strategies substantially improved the stability of curcumin. Because of the unique UV-blocking capacity of blue pigment, crosslinked samples retained 20% more curcumin than control samples. With the enhanced stability of curcumin, the crosslinked SBP-curcumin complexes could be a functional food ingredient used in functional drinks, baked food, and jelly food.

Background: Skip lymph node metastasis (SLNM) refers to lateral lymph node metastasis (LLNM) without involving central lymph node (CLN). Some microscopic nodal positivity may be difficult to detect before surgery due to atypical imaging characteristics. These patients are misdiagnosed as having clinically node-negative (cN0) papillary thyroid cancer (PTC) even after central lymph node dissection, leading to a high risk of developing LNM after surgery. Current prediction models have limited clinical utility, as they are only applicable to predict SLNM from clinically node-positive (cN+) PTC, not cN0 PTC, and this has little impact on treatment strategies., Objectives: This study aimed to establish a nomogram for preoperatively assessing the likelihood of SLNM in cN0 PTC patients with increased risk of LNM, thus optimizing their therapeutic options., Material and Methods: The records of 780 PTC patients undergoing thyroidectomy along with bilateral central lymph node dissection were retrospectively reviewed. The cN0 patients with postoperative LLNM (occult SLNM) and cN+ patients without central lymph node metastasis (CLNM) (typical SLNM) were included in the SLNM group (n = 82). The CLNM-negative cN0 patients without postoperative LLNM were assigned to the non-SLNM group (n = 698). The independent correlates of SLNM constituted the nomogram for determining the likelihood of SLNM in high-risk cN0 PTC patients., Results: The independent correlates of SLNM were age (hazard ratio (HR) = 1.016), tumor location (HR = 1.801), tumor size (HR = 1.528), and capsular invasion (HR = 2.941). They served as components in the development of the nomogram. This model was verified to present acceptable discrimination. It showed good calibration and a decent net benefit when the predicted probability was <60%., Conclusions: We developed a nomogram incorporating preoperative clinical data to predict the probability of SLNM development in high-risk cN0 PTC patients, which contributed to their optimized treatment options.

Emerging studies suggest the significance of broadening the benefit of anti-programmed cell death 1 (PD-1) therapy for lung cancer. The anti-angiogenic agents have been reported to alter the tumor microenvironment and contributes to efficiency of anti-PD-1 therapy. This study aims to investigate whether the anti-angiogenic agent rhamnazin enhances the efficacy of anti-PD-1 therapy in lung cancer. In Lewis lung carcinoma (LLC) xenografts, the combination of rhamnazin and anti-PD-1 treatment suppressed tumor growth, elevated the infiltration of CD4 + T and CD8 + T cells in tumors and up-regulated interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and granzyme B. Furthermore, the combination reduced programmed cell death ligand 1 (PD-L1) expression in tumors more significant than anti-PD-1 treated group. In LLC cell experiments, rhamnazin inhibited vascular endothelial growth factor A (VEGFA)-stimulated vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation and PD-L1 expression, whereas VEGFR2 overexpression reversed these trends. T cell proliferation and cytotoxic factor production were evaluated after co-culturing with non-small cell lung cancer (NSCLC) H1975 cells. Rhamnazin promotes T cell proliferation and up-regulated IFN-γ, TNF-α and granzyme B in the co-culture system, while VEGFR2 overexpression abrogated these changes. These data suggest that rhamnazin enhances anti-tumor effect of anti-PD-1 therapy for lung cancer in mice via inhibition of PD-L1 expression.

Electroreductive ring-opening carboxylation of cycloketone oxime esters with atmospheric carbon dioxide is reported. This reaction proceeded under simple constant current conditions in an undivided cell using glassy carbon as the cathode and magnesium as the sacrificial anode, providing substituted γ- and δ-cyanocarboxylic acids in moderate to good yields. Electrochemically generated cyanoalkyl radicals and cyanoalkyl anion are proposed as the key intermediates.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment., Methods: The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs., Findings: The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice., Interpretation: In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN., Funding: This study was funded by the National Natural Science Foundation of China81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu ProvinceBK20191253; Major Project of "Science and Technology Innovation Fund" of Nanjing Medical University2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu ProvinceBE2019732; Nanjing Special Fund for Health Science and Technology DevelopmentYKK19170., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1 -/- mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response., (© 2023. The Author(s).)

Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation., (© 2022 The Authors.)

We describe an extensively drug-resistant Klebsiella michiganensis strain, Kmfe267, which was originally isolated from a renal abscess patient. The strain carries the blaNDM-5 gene, which encodes a New Delhi metallo-β-lactamase. The complete genome of the strain contains a 5.9-Mb chromosome and 5 plasmids.

Background: Whether combined CsA with androgen therapy was superior to androgen therapy alone in NSAA remains controversial. This study aimed to assess the efficacy and safety of combined therapy versus androgen therapy for NSAA patients using a meta-analytic approach., Methods: An electronic database of PubMed, EmBase, Cochrane library, CNKI, VIP, and Wanfang was systematically searched for randomized controlled trials (RCTs) from their inception to February 2020. The primary endpoint was effective rate, while the secondary endpoints included white blood cell (WBC), hemoglobin, platelet, and potential adverse events. The pooled results from included trials were calculated with the random-effects model., Results: Forty-three RCTs recruited 2610 NSAA patients for the final quantitative meta-analysis. We noted that combined therapy was associated with an increased incidence of effective rate than androgen therapy alone (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.29-1.41; P  < 0.001). Moreover, patients treated with combined therapy were associated with higher WBC (weighted mean difference [WMD]: 1.22; 95%CI: 0.94-1.49; P  < 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86-17.01; P  < 0.001), and platelet (WMD: 8.65; 95%CI: 7.05-10.24; P  < 0.001). Finally, the pooled incidence of hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage were 0.35 (95%CI: 0.22-0.48), 0.24 (95%CI: 0.15-0.32), 0.22 (95%CI: 0.10-0.35), 0.19 (95%CI: 0.14-0.25), and 0.06 (95%CI: 0.01-0.11), respectively., Conclusions: This study found that combined CsA with androgen therapy was superior to androgen therapy alone for Chinese patients with NSAA, and the most common adverse of combined therapy included hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage.

To investigate the role of the sugar transporter MAL31 on pullulan biosynthesis, the coding gene mal31 was respectively disrupted and overexpressed in the parental strain A. pullulans CCTCC M 2012259 to construct mutants of A. pullulans Δmal31 and A. pullulans Mal31. Batch pullulan production significantly decreased by 69.1 % in A. pullulans Δmal31 but increased by 15.9 % in A. pullulans Mal31, as compared to the parental strain. We performed kinetics analysis, assays of key enzymes, determination of intracellular UDPG, NADH, and ATP contents, and measurement of transcriptional levels of genes associated with pullulan biosynthesis and excretion. The results confirmed that the mal31 disruption decreased the glucose consumption rate, decreased the formation rate and titer of pullulan, but increased the intracellular UDPG supply for β-glucan accumulation. In contrast, the mal31 overexpression increased the transcriptional levels of genes associated with pullulan biosynthesis, and accelerated the rates of glucose consumption and pullulan formation, thereby increased pullulan production. Our findings revealed that MAL31 is involved in the transport of precursors for pullulan biosynthesis. This study provides an accurate operating site for genetic modification of A. pullulans for improving pullulan production and also presents a feasible technique route for the overproduction of other polysaccharides., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although people are more and more aware of the cardiotoxicity caused by immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, its incidence rate has not been systematically analyzed. This study aims to evaluate the incidence of cardiotoxicity related to the ICI therapies for lung cancer, so as to enhance clinicians' attention to cardiotoxicity, implement proper prevention and intervention for high-risk patients, and minimize the risk of cardiac dysfunction during and after completion of therapy., Methods: We conducted a systematic literature search for relevant publications in PubMed and Scopus from inception to 19 April 2022. Pooled incidence and risk ratios with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated., Results: A total of 37 studies covering 38 trials, including 14,342 patients, were identified. The pooled risk ratios of incidence of any cardiac AEs were 1.944 [95% CI 0.8-4.725] (Single ICI versus chemotherapy), 1.677 [95% CI 1.065-2.64] (Single ICI plus chemotherapy versus chemotherapy), and 0.478 [95% CI 0.127-1.798] (Single ICI versus Dual ICI). The incidence of myocarditis and arrhythmia were 0.003[95%CI 0.002-0.006] and 0.014[95%CI 0-0.037], respectively., Conclusion: Single ICI did not increase the risk of cardiotoxicity compared with chemotherapy, and single ICI plus chemotherapy increased the risk of cardiotoxicity by 67% compared with chemotherapy alone. Combination immunotherapy did not increase the risk of cardiotoxicity compared with single ICI., (© 2022. The Author(s).)

The relationship between hemiplegic shoulder pain (HSP) and subluxation is unclear. This study aimed to determine the differences of magnetic resonance imaging (MRI) findings in HSP patients with or without subluxation after stroke, and to analyze the etiology of shoulder pain. This retrospective study included 53 patients with HSP after stroke from September 2013 to February 2020. Patients underwent MRI of the shoulder because of shoulder pain. Clinical characteristics, including age, sex, stroke duration, body mass index, stroke type, visual analog scale score, Brunnstrom stage, and MRI arthrography findings of the affected shoulder, were recorded. Patients were classified into the glenohumeral subluxation (GHS) group ( n = 27) or non-glenohumeral subluxation (nGHS) group ( n = 26). We found that patients with HSP may be prone to bursa effusion, rotator cuff injury, ligament injury, and cartilage injury, even though there was no significant difference between the GHS and nGHS groups. MRI revealed 14 cases of long bicipital tendon-glenoid labrum injury (51.8%) in the GHS group and 6 cases (23.1%) in the nGHS group ( p = 0.030). We also found 10 cases (37%) of glenoid labrum injury in the GHS group and 2 cases (7.7%) in the nGHS group ( p = 0.026). Eight cases (29.6%) and 1 case (3.8%) of bone marrow edema were found in the GHS and nGHS groups, respectively ( p = 0.033). Compared with painful hemiplegic shoulder patients without subluxation, patients with subluxation may be more susceptible to some injuries, such as long bicipital tendon-glenoid labrum injury, glenoid labrum injury, and bone marrow edema. During rehabilitation, physicians need to pay attention to these injuries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Zhang, Xu, Wang, Wang, Jia and Zhang.)

Aim: To observe the clinical effect of pars plana vitrectomy (PPV) and silicone oil filling surgery combined with intraoperative posterior scleral staphyloma (PS) marginal retinal photocoagulation in the treatment of high myopic macular hole retinal detachment (MHRD) with PS., Methods: This was a retrospective clinical study. From May 2017 to March 2020, 62 MHRD patients with PS (62 eyes) were enrolled in the study. Patients were divided into 23G PPV combined with PS marginal retina intraoperative photocoagulation group (combined group) and conventional surgery group (conventional group), with 31 eyes in each. Triamcinolone acetonide and indocyanine green were used to remove the epiretinal membrane and the posterior macular inner limiting membrane (ILM). In the combined group, 2 to 3 rows of retinal photocoagulation were performed on the edge of the PS. The patients were followed up for an average of 8.34±3.21mo. The first retinal reattachment rate, macular hole closure rate, Duration of silicone oil tamponade, best corrected visual acuity (BCVA) and average number of operations were observed and compared between the two groups., Results: The first retinal reattachment rates of the eyes in the combined group and the conventional group were 96.7% (29/31) and 67.7% (21/31), respectively ( χ 2 =6.613, P =0.010). The macular hole closure rates in the combined group and the conventional group were 74.2% (23/31) and 67.7% (21/31), respectively ( χ 2 =0.128, P =0.721). The Duration of silicone oil tamponade of the patients in the combined group was lower than that of the routine group ( t =-41.962, P ≤0.001). Postoperative logMAR BCVA values of patients in the combined group and the conventional group were 1.27±0.12 and 1.26±0.11, compared with the logMAR BCVA before surgery, each group was improved ( t =19.947, t =-19.517, P ≤0.001, P ≤0.001). There was no significant difference in the logMAR BCVA between the eyes of the two groups ( t =-0.394, P =0.695). The average numbers of operations on the eyes in the conventional group and the combined group were 2.39±0.62 and 2.06±0.25 times, the combined group had fewer operations on average ( t =-2.705, P =0.009)., Conclusion: Intraoperative PPV treatment of MHRD with PS combined with PS marginal endolaser photocoagulation can effectively increase the rate of retinal reattachment after the first operation, reduce the number of repeated operations, and reduce the postoperative duration of silicone oil tamponade., (International Journal of Ophthalmology Press.)

The objective of this study was to investigate whether brain volume changes occur in patients with chronic ankle instability (CAI) using voxel-based morphometry and assessing correlations with clinical tests. Structural magnetic resonance imaging data were prospectively acquired in 24 patients with CAI and 34 healthy controls. CAI symptoms and pain intensity were assessed using the Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS). The gray matter volume (GMV) of each voxel was compared between the two groups while controlling for age, sex, weight, and education level. Correlation analysis was performed to identify associations between abnormal GMV regions and the FAAM score, AOFAS score, VAS score, disease duration, and body mass index. Patients with CAI exhibited reduced GMV in the right precentral and postcentral areas, right parahippocampal area, left thalamus, left parahippocampal area, and left postcentral area compared to that of healthy controls. Furthermore, the right parahippocampal (r = 0.642, p = 0.001), left parahippocampal (r = 0.486, p = 0.016), and left postcentral areas (r = 0.521, p = 0.009) were positively correlated with disease duration. The left thalamus was positively correlated with the CAIT score and FAAM activities of daily living score (r = 0.463, p = 0.023 and r = 0.561, p = 0.004, respectively). A significant positive correlation was found between the local GMV of the right and left parahippocampal areas (r = 0.487, p = 0.016 and r = 0.763, p < 0.001, respectively) and the AOFAS score. Neural plasticity may occur in the precentral and postcentral areas, parahippocampal area, and thalamus in patients with CAI. The patterns of structural reorganization in patients with CAI may provide useful information on the neuropathological mechanisms of CAI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Xing, Chen, Zhang, Qiu, Jia, Zhang and Yu.)

Background: Diabetes is a metabolic disease with a high complication rate. Diabetic foot ulcers (DFUs) seriously affect the quality of life of patients. A total of 15%-20% of diabetic patients develop DFUs, which heal with difficulty over a long time and can result in amputation and disability. Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases. Ruyi Jinhuang powder (RHP) is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice., Aim: To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin (HE) staining. The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry (GC-MS), and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism., Methods: Sprague Dawley rats were injected with streptozotocin to establish the DFU model. HE staining was used to observe the wound tissue under an electron microscope. The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction, and then, GC-MS and ultra-performance liquid chromatography-MS were used to separately identify the chemical constituents. In addition, the "herb-component-target" link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information, and the molecular docking of important components and key targets was performed in Discovery Studio software. Cytoscape software was used to visualize and analyze the relationship between the chemical composition, targets and Traditional Chinese Medicine network., Results: RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells. A total of 89 chemical components were obtained by GC-MS. Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU, of which the important components were luteolin, trans caryophyllene, ar-turmerone, palmitic acid, methyl palmitate, gallic acid, demethoxycurcumin, berberine, and rheic acid. The key targets were posttranscriptional silencing, topoisomerase II alpha, muscarinic acetylcholine receptor M2, interleukin 6, tumor necrosis factor and retinoic X receptor alpha, and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway, neuroactive ligand-receptor interactions, and the forkhead box O signaling pathway., Conclusion: Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance, altering the nervous system and immune system, participating in inflammatory responses and regulating cell proliferation, differentiation and apoptosis through other specific mechanisms., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)